MATRIX COMPOSITION FOR TISSUE REINFORCEMENT AND/OR FILLING

Abstract: The present invention relates to a matrix composition comprising a fibre of degradable biocompatible polymer. The matrix composition is rigid enough at 37 DEG C to hold against a negative tissue pressure of at least 2 cm H2O and at the most 50 cm H2O, and elastic enough to regain its shape after mechanical deformation. The matrix composition is used for tissue reinforcement nad/or filling.

Description: Matrix composition for tissue reinforcement an /υr filling The present invention relates to a matrix composition for tissue reinforcement and/or filling. Within the field of reconstructive surgery there is often a need to fill out or reinforce tissue. Normally bone from for example the iliac crest is transplanted to the area to be reinforced. This means that two surgical operations have to be performed on the same patient. Moreover, it is often desired to obtain a space for regenerating tissue such as nerves in nerve sheath or bone after surgery in the skull. Modern membrane technology has enabled separation and isolation of tissue sections leading to development of the correct tissue type. This is for instance the case in controlled bone growth within oral surgical reconstruction or growth of skull and vertebra in neurosurgical reconstructions. A common complication in connection with these membrane implanta¬ tions is that the tissue space to be regenerated collapses by the outer pressure effect in interaction with the so called negative tissue pressure. This condition has been observed and a number of methods have been developed to counteract these effects. For instance membranes have been designed being manufactured with molded spacers as described e.g. in WO90/07308. Furthermore, bone cavities have been filled out with hydroxyapa- tite or deproteinized bone. In further other examples the membrane has been made extremely hard and strong to counteract collapse (for example BioFix). In all these cases, considerable inconveniences have arisen in use. Thus, a too hard membrane causes penetration through the mucous membrane or migrates in the body. Molded spacers have to be formed being perfectly adapted to the supporting membrane. Other examples, such as different types of filling materials, prevent the development of natural tissues. The present invention solves the above problems by providing a fiber comprising matrix composition creating a non-collapsible space in the tissue. The composition according to the invention is rigid enough at 37 β C to hold against a negative tissue pressure of at least 2 cm H 2 0 and at the most 50 cm H 2 0, and elastic enough to regain its shape following mechanical deformation. The matrix is designed to follow the tissue closely. The solid implant pressure against which the matrix should hold mustn't be below the normal negative liquid pressure in the body, i.e. about 0,5-5 cm H 2 0. The applicant has found that a negative liquid pressure of 2 cm H 2 0 is a suitable lower limit for most applica¬ tions. On the other hand, the solid implant pressure against which the matrix should hold, must not be higher than about 50 cm H 2 0 since such materials gives a too hard matrix which will penetrate the tissue and begin to migrate. Preferably, the polymer fiber of the matrix composition according to the present invention is selected from the group consisting of polymeric butyric acid, polyglycolide and co-polymers thereof, polyactides and co-polymers thereof, poly-β-hydroxybutyrate and co-polymers thereof, poly-p-dioxanone, poly-δ-valerolactone, poly-€-caprolactone, methyl-metacrylate-N-vinyl pyrrolidine co- polymers, polyester amides, polyesters of oxalic acid, poly- dihydropyranes, polyalcyl-2-cyanoacrylates, polyurethanes, polyvinylalcohol, polypeptides, poly-β-maleic acid and poly-β- alcanoic acids and alginates. The fibres of the matrix composition are made by an extruding process under known conditions. Another way of producing the fibres is by using the method described in applicants copending international application no. WO 92/21326, to which is referred. The the solid implant pressure of the matrix composition according to the invention is measured by using the following method. For the measurement, there is used a balloon method similar to what is described by A.C. Guyton in Circ. Res. 16:452, 1965. Fifty mg of the solid matrix is introduced in a small rubber balloon. The balloon is filled with 50 ml of a buffered physiological water at 37°C and connected to a graded tube. The balloon with its content is put into a thermostated water bath (37 β C) and the tube is fixed to a meter slide. The measurements are carried out by lowering the tube step by step thereby creating a negative fluid pressure in the balloon. The corre¬ sponding steady state change in volume at a fixed pressure decrease is read on the water column. The solid matrix pressure (P 50 ) is the pressure under which the matrix can keep 50% of the free fluid volume as measured as the difference between the volume at zero pressure difference (V Bajt ) and at maximum concen¬ tration of the balloon (V_, in ). Another essential feature of the matrix composition according to the invention is that it is elastic enough to regain its shape after mechanical deformation. According to another embodiment of the invention, the composition comprises therapeutically active agents, e.g. pharmacologically active agents such as growth modifying, bacteriostatic and cytostatic agents, and suitable combinations thereof. Preferably, the therapeutic agents are incorporated in the composition by impregnating the fibres with a solution active agents. The invention will be described below in connection with some non-limiting examples. EXAMPLE 1 To fill out a pit caused by an old vaccination on the upper arm of a young woman the skin was opened, the damaged skin section was removed and the subcutis tissue was filled out with a matrix made of bovine collagen fibers, which had previously been radiation sterilized for obtaining the correct properties. The healing occurred without complications and a natural tissue had developed upon control three months later. The collagen material showed the following characteristics "in vitro" in physiological saline at 37°C after incubation for 24 hours. Solid implant pressure: 8 cm H 2 0. Time for reshape following 50% deformation: 7 minutes. EXAMPLE 2 An elderly woman had lost a large part of the edge of the alveolar bone and had begun to have problems in keeping her dentures. The mucous membrane was opened and small holes were drilled so that contact with the bone marrow was established. A ridge of extruded lactide polymer matrix was applied and over the matrix there was arranged a membrane of a copolymer of lactide/- glycolide covered with a thin layer of encapsulated tissue growth factor TGF-βl, in such a way that the matrix was completely covered. The dentures were designed so that a recess prevented a constant pressure initially over the surgical area. After three months a hard tissue could be palpated. After six months there existed a bone on growth, which still kept its shape one year after the surgery. In vitro measurements of the matrix 24 hours after incubation in 37"C water showed a solid implant pressure of 22 cm H 2 0 and a return to the original shape after a 50% compression in 4 minutes. EXAMPLE 3 In connection with planning for a dental fixture implantation it was found that the bone edge was too thin to completely cover a fixture. In connection with applying thereof, a matrix according to the invention and a membrane were placed over the bare threads on both sides of the bone edge. After six months the mucous membrane over the so called cover screw was opened and upon inspection of the area it was found that hard bone tissue had developed over and against the fixture. After another six months the fixture was still firmly anchored and the bone on-growth intact. "In vitro" control of the matrix was after incubation in 37 β C water for 24 hours. Solid implant pressure: 18 cm H 2 0. Reshape after 50% compression: 2 minutes. EXAMPLE 4 In connection with reconstruction of the skull bone after a traffic injury it was desired to regenerate the skull bone on the left edge of the front side. A raw connective tissue had been developed and after two years no bone development had occurred. A gap, 20 mm long and 6 mm wide, needed bridging with bone. The raw connective tissue was removed and contact with intact bone surface and bone marrow was established. The gap was filled with polylactide matrix and also a copolymer membrane (according to Example 2) was positioned covering the gap with an overlap of 10 mm. The membrane was attached and fixed with a degradable cement of copolymer. Upon a later control of the bone tissue the gap was found to be filled with bone-like hard tissue while the remaining raw connective tissue was intact. In the above examples 2-4 and in other cases when it is required to cover the matrix, the patient's own as well as materials especially produced for this purpose may be used. In the latter case, a membrane and sealing agent of biodegradable type are preferably used as described in the applicant's international patent application publication No. W093/00936.

Claims: CLAIMS 1. A tissue reinforcing and/or filling matrix composition, comprising fibres of degradable biocompatible polymer and being rigid enough at 37 β C to hold against a negative tissue pressure of at least 2 cm H 2 0 and at the most 50 cm H 2 0, and elastic enough to regain its shape after mechanical deformation. 2. A composition according to claim 1, wherein the polymer is selected from the group consisting of polymeric butyric acid, polyglycolide and co-polymers thereof, polyactides and co- polymers thereof, poly-β-hydroxybutyrate and co-polymers thereof, poly-p-dioxanone, poly-δ-valerolactone, poly-e-caprolactone, methyl-metacrylate-N-vinyl pyrrolidine co-polymers, polyester amides, polyesters of oxalic acid, polydihydropyranes, poly- alcyl-2-cyanoacrylates, polyurethanes, polyvinylalcohol, poly- peptides, poly-β-maleic acid and poly-β-alcanoic acids and alginates. 3. A composition according to claims 1 or 2, also comprising a biologically degradable polymeric membrane. 4. A composition according to claim 3, also comprising a biologically degradable polymeric cement. 5. A matrix composition according to anyone of the claims 1-4, also comprising therapeutically active agent(s). 6. A matrix composition according to claim 5, wherein the active agent is selected among the group consisting of growth modifying, bacteriostatic and cytostatic agents or suitable combinations thereof. 7. Use of a matrix composition according to any of the claims 1-6 for tissue reinforcement and/or filling. 8. A method of tissue reinforcement and/or filling, comprising reinforcing and/or filling injured tissue with a composition according to anyone of the claims 1-7.

Inventors: AAGERUP BENGT, AAGERUP, BENGT
Applicants: AAGERUP BENGT, MEDINVENT SA, AAGERUP, BENGT, MEDINVENT
Application year: 1994
Main classification: A61L27
IPC codes: A61L27, A61L31